The objectives of this study are to ascertain biological, physiological and clinical mechanisms of male reproductive disorders and to provide rational strategies of treatment for men with reproductive disease. This project represents a continuum of research begun in 1970 and includes studies of 1) the hormonal regulation of spermatogenesis in gonadotropin deficient men, 2) biology of sperm function, 3) adverse effects of cancer therapy on gonadal function, 4) evaluation of treatment of men with reproductive disorders and 5) the role of sex steroids in regulation of gonadotropin secretion. Major findings from studies performed during the past year have shown 1) that early exposure of hypogonadotropic men to FSH (with hCG) augments testicular growth and onset of sperm production, 2) that epididymal glycoproteins, which normally coat sperm and which are required for fertilization, are reduced on sperm from some men with idiopathic infertility, 3) that testicular exposure to fractionated radiation above 50 rads leads to germinal depletion with increased serum FSH levels and that above 100 rads leads to prolonged testicular injury, 4) that, contrary to a recent report, no subtle androgen receptor deficiency is found in cultured genital skin fibroblasts from men with idiopathic azoospermia and that treatment with human chorionic gonadotropin plus testolactone (an aromatase inhibitor) to augment testicular androgen production does not improve sperm production; and 5) that GnRH and orchiectomy differentially regulate LH subunit apoprotein and carbohydrate biosynthesis in studies of rat pituitary tissue.